期刊
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
卷 139, 期 5, 页码 1900-1911出版社
AMER CHEMICAL SOC
DOI: 10.1021/jacs.6b11324
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资金
- National Institutes of Health, General Medical Sciences [R01GM090260, R15GM114787]
- U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences [DE-FG02-04ER15563]
- U.S. Department of Energy (DOE) [DE-FG02-04ER15563] Funding Source: U.S. Department of Energy (DOE)
Coproheme decarboxylase catalyzes two sequential oxidative decarboxylations with H2O2 as the oxidant, coproheme III as substrate and cofactor, and heme b as the product. Each reaction breaks a C-C bond and results in net loss of hydride, via steps that are not clear. Solution and solid-state structural characterization of the protein in complex with a substrate analog revealed a highly unconventional H2O2 activating distal environment with the reactive propionic acids (2 and 4) on the opposite side of the porphyrin plane. This suggested that, in contrast to direct C-H bond cleavage catalyzed by a high-valent iron intermediate, the coproheme oxidations must occur through mediating amino acid residues. A tyrosine that hydrogen bonds to propionate 2 in a position analogous to the substrate in ascorbate peroxidase is essential for both decarboxylations, while a lysine that salt bridges to propionate 4 is required solely for the second. A mechanism is proposed in which propionate 2 relays an oxidizing equivalent from a coproheme compound I intermediate to the reactive deprotonated tyrosine, forming Tyr(center dot). This residue then abstracts a net hydrogen atom (H-center dot) from propionate 2, followed by migration of the unpaired propionyl electron to the coproheme iron to yield the ferric harderoheme and CO2 products. A similar pathway is proposed for decarboxylation of propionate 4, but with a lysine residue as an essential proton shuttle. The proposed reaction suggests an extended relay of heme-mediated e(-)/H+ transfers and a novel route for the conversion of carboxylic acids to alkenes.
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